Protective Effect of Resveratrol on Exercise-induced Kidney Injury in Rats by Regulating Keap1-Nrf2 Signaling Pathway

Objective: To investigate the protective mechanism of resveratrol on exercise-induced kidney injury in rats. Methods: Thirty-two 7-week-old SPF-grade male SD rats were randomly assigned to four groups: control group (CONT, n=8), resveratrol group (RESV, n=8), exercise-induced kidney injury model group (EIKIM, n=8), and resveratrol-treated exercise-induced kidney injury group (REIKIM, n=8). Rats in groups EIKIM and REIKIM underwent high-intensity treadmill training to establish a model of exercise-induced kidney injury. During the four-week training, rats in groups RESV and REIKIM were administered resveratrol solution intragastrically at a dosage of 150 mg/kg·bw and a volume of 5 mL/kg, 1 h prior to each training session, and the remaining rats received an equal volume of solvent. Blood and kidney samples were obtained 24 h post the final training session. Kidney morphology was assessed using HE staining. Levels of serum creatinine (Cr) and urea nitrogen (UN), renal kelch-like ECH-associated protein-1 (Keap1), nuclear factor-E2-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) mRNA and protein expression levels, phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) protein expression level, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GSH-ST) activity, levels of malondialdehyde (MDA), reactive oxygen species (ROS), apoptosis, B cell lymphoma-2 protein (Bcl-2), bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase-9 (Caspase-9), and cysteinyl aspartate specific proteinase-3 (Caspase-3) protein expression were detected. Results: After 4 weeks of high-intensity treadmill training, significant renal pathological changes of rats were observed in group EIKIM compared to group CONT, with increased levels of serum Cr and UN, renal Keap1 mRNA and protein expression, MDA, ROS, apoptosis, Bax, Caspase-9, Caspase-3 protein expression and Bax/Bcl-2 ratio (P<0.01), and decreased levels of renal Nrf2, NQO1, HO-1 mRNA and protein expression, SOD CAT and GSH-ST activity, p-Nrf2, Bcl-2 protein expression and p-Nrf2/Nrf2 ratio (P<0.01). In contrast, after 4 weeks of resveratrol treatment, rats in group REIKIM exhibited significant improvements in renal pathology compared to group EIKIM, with decreased levels of serum Cr and UN, renal Keap1 mRNA and protein expression, MDA, ROS, apoptosis, Bax, Caspase-9, Caspase-3 protein expression and Bax/Bcl-2 ratio (P<0.05 or P<0.01), and increased levels of renal Nrf2, NQO1, HO-1 mRNA and protein expression, SOD, CAT and GSH-ST activity, p-Nrf2, Bcl-2 protein expression and p-Nrf2/Nrf2 ratio (P<0.05 or P<0.01). Conclusions: Resveratrol can activate the Keap1-Nrf2 signaling pathway of rats subjected to high-intensity exercise effectively, suppress oxidative stress and apoptosis, thereby protecting the integrity of renal structure and function.